CXCR1 as a predictor of response to treatment with epidermal growth factor receptor therapeutic

Abstract

There is provided a molecular marker CXCR1 for predicting response and survival in subjects afflicted with cancer who would benefit from treatment with and Epidermal Growth Factor Receptor (EGFR) targeted therapeutic.

The invention claimed is: 
     
       1. A method of predicting response in a cancer subject to treatment with an Epidermal Growth Factor Receptor (EGFR) targeted therapeutic, wherein the EGFR targeted therapeutic is an EGFR targeted antibody or small molecule EGFR inhibitor, the method comprising using CXCR1 as a biomarker, comprising the steps of
 determining in a tumour sample from the cancer subject an expression level of CXCR1; 
 comparing the determined expression level of CXCR1 in the tumour sample from the cancer subject with an expression level of CXCR1 in a Control, wherein when the expression level of CXCR1 determined in the tumour sample from the cancer subject is increased from that of the expression level of CXCR1 in the Control the expression level of CXCR1 is indicative the cancer subject would benefit from treatment with an Epidermal Growth Factor Receptor targeted therapeutic; and 
 administering a therapeutically effective amount of an EGFR targeted therapeutic to the subject if the subject has an expression level of CXCR1 increased from that of an expression level of a Control. 
 
     
     
       2. The method as claimed in  claim 1  wherein the Control is a control population of cancer subjects and the expression level of CXCR1 in the Control is the median expression level of CXCR1 in the control population. 
     
     
       3. The method as claimed in  claim 1 , wherein the tumour is selected from the group consisting of a colorectal tumour, a NSCLC tumour, a head and neck tumour, and an ovarian tumour. 
     
     
       4. The method as claimed in  claim 1 , wherein the Epidermal Growth Factor Receptor targeted therapeutic is selected from at least one of Cetuximab, Panitumumab, Gefitinib, and Tarceva. 
     
     
       5. The method as claimed in  claim 1  wherein the Epidermal Growth Factor Receptor targeted therapeutic is at least one of Cetuximab or Panitumumab. 
     
     
       6. The method as claimed in  claim 5  wherein the Epidermal Growth Factor Receptor targeted therapeutic is Cetuximab. 
     
     
       7. The method as claimed in  claim 5  wherein the Epidermal Growth Factor Receptor targeted therapeutic is at least one of Cetuximab or Panitumumab and is provided as a monotherapy. 
     
     
       8. The method as claimed in  claim 5 , wherein the subject is treated with at least one of Cetuximab or Panitumumab in combination with a clinically-approved conventional cytotoxic chemotherapy agent. 
     
     
       9. The method as claimed in  claim 1 , wherein the step of determining the expression level comprises as least one of:
 determining a protein expression level of CXCR1; 
 determining a level of mRNA encoding CXCR1; 
 determining a copy number of CXCR1; and 
 determining an expression level of any non-coding or coding polymorphism within a nucleotide sequence CXCR1. 
 
     
     
       10. The method as claimed in  claim 1 , wherein the tumor sample is a tumor tissue sample. 
     
     
       11. The method of  claim 1  further comprising the step of determining that the subject is responsive to the EGFR targeted therapeutic by measuring the level of CXCR1 in a tumor sample in the subject after administration of the EGFR targeted therapeutic.